Nucleic acids encoding antibodies against PD-1

Abstract

This disclosure provides antibodies and antigen-binding fragments that can act as agonists and/or antagonists of PD-1 (Programmed Death 1), thereby modulating immune responses in general, and those mediated by TcR and CD28, in particular. The disclosed compositions and methods may be used for example, in treating autoimmune diseases, inflammatory disorders, allergies, transplant rejection, cancer, and other immune system disorders.

1. An isolated nucleic acid encoding an antibody comprising:
 (i) a V H  domain that comprises three CDRs having the amino acid sequences as set out in:
 (a) SEQ ID NOs: 23, 24, and 25, 
 (b) SEQ ID NOs: 29, 30, and 31, 
 (c) SEQ ID NOs: 35, 36, and 37, or 
 (d) SEQ ID NOs: 50, 51, and 52; or 
 
 (ii) a V L  domain that comprises three CDRs having the amino acid sequences as set out in:
 (e) SEQ ID NOs:26, 27, and 28, 
 (f) SEQ ID NOs: 32, 33, and 34, 
 (g) SEQ ID NOs:38, 39, and 40, or 
 (h) SEQ ID NOs:53, 54, and 55, 
 
 
       wherein the antibody specifically binds an epitope within the extracellular domain of human or mouse PD1. 
     
     
       2. An expression vector comprising the nucleic acid of  claim 1 . 
     
     
       3. An isolated host cell comprising the vector of  claim 2 . 
     
     
       4. The nucleic acid of  claim 1 , wherein the V H  domain comprises the amino acid sequence SEQ ID NO:6, 10, 14, or 47; and the V L  domain comprises the amino acid sequence SEQ ID NO:8, 12, 16, or 49. 
     
     
       5. The nucleic acid of  claim 4 , wherein the nucleic acid comprises a nucleotide sequence selected from the group consisting of
 (a) SEQ ID NOs: 5, 9, 13, and 46; or 
 (b) SEQ ID NOs: 9, 11, 15, and 48. 
 
     
     
       6. A method of making an antibody that specifically binds with PD-1, the method comprises: (a) providing the expression vector of  claim 2 ; (b) expressing the antibody encoded by the expression vector in a host cell; and (c) recovering the antibody.